Antidepressants can counter depression, lessen fatigue, and improve the
quality of life of cancer patients who have a major depression, researchers
However, a study of one SSRI, sertraline, showed that it did not help
advanced cancer patients whose depressive symptoms are less severe.
It was headed by Martin Stockler, M.D., a medical oncologist and associate
professor of cancer medicine and clinical epidemiology at the University of
Sydney in Australia. Results were published in the June 4 early online
publication of The Lancet Oncology.
This randomized, double-blind, placebo-controlled, multicenter included 189
patients with advanced cancer. All had filled out a Patient Disease and
Treatment Assessment Form while visiting their oncologists. The form asked the
patients to evaluate themselves on seven aspects of well-being on a scale of 0
to 10. Zero meant "no trouble at all," 1 through 3"
mild," 4 through 6 "moderate," 7 through 9"
severe" and 10 "the worst I can imagine." All had
given themselves a score of 4 or higher regarding depression, anxiety, and
fatigue—a criterion for participating in the study.
None, however, was thought by his or her oncologist to have major
depression. Oncologists recruiting patients for the trial had been instructed
that if they suspected that any patients had major depression, they should
refer them to the psychiatrist at their center who was participating in the
trial. If the patients were found by the psychiatrist to have major
depression, they were treated and not recruited into the study.
Half of the 189 subjects were assigned to receive, on a daily basis, 50 mg
of the SSRI antidepressant sertraline, and half were assigned to receive a
placebo, to be continued indefinitely. Concomitant anticancer treatments as
well as supportive treatments—for example, the prescribing of opioids or
antiemetics, or referral to a psychologist, social worker, or palliative-care
team—were given according to standard local practice.
Subjects were evaluated at the start of the trial and at four, eight, 12,
16, 26, 39, and 52 weeks later for depression, anxiety, fatigue, and overall
quality of life.
Multiple instruments were used to document outcomes. For example, the
Center for Epidemiologic Studies Depression scale, a validated yardstick for
identifying depression in the general population, was used to evaluate
depression in the subjects. The Hospital Anxiety and Depression Scale, which
assesses anxiety and depression in those who are medically ill, was used to
evaluate anxiety. At the start of the study one-fourth of the subjects had
scores on the Center for Epidemiologic Studies Depression scale consistent
with clinical depression, and 8 percent had scores on the Hospital Anxiety and
Depression Scale consistent with anxiety.
Subjects were also assessed on length of survival, which was calculated
from the date of their randomization into the trial to the date of their death
from any cause. Finally, results for the antidepressant and control groups
Antidepressant treatment was found to have no significant benefit over a
placebo in reducing subjects' depression, anxiety, or fatigue, or in improving
their overall quality of life, at four or eight weeks after the trial started.
The same was the case when results from four and 12 weeks into the trial were
compared and when results from four and 52 weeks were compared. In fact, even
subjects with the worst scores at the start of the study did not appear to
benefit from taking sertraline. The only advantages that sertraline seemed to
confer over placebo were in reducing irritability, cough, sleep difficulties,
and "difficulty in looking after myself."
When assessing survival duration, the researchers found no significant
difference between the antidepressant group and the placebo group. Moreover,
the groups did not differ in the number of deaths due to cancer progression or
in the number of deaths occurring earlier than expected.
Thus "sertraline did not improve symptoms, well-being, or survival in
patients with advanced cancer who did not have a major depression," the
researchers concluded, "and should be reserved for those with a proven
indication." They also noted their doubt "that a higher dose of
sertraline, or a different SSRI, would have been more effective in our target
population." "However, we cannot rule out these
possibilities," they acknowledged.
"This well-conducted study from Australia points out the problems of
control of psychological symptoms in advanced cancer that stem from the cancer
itself and psychological responses," Jimmie Holland, M.D., chair of
psychiatric oncology at Memorial Sloan-Kettering Cancer Center in New York
City, told Psychiatric News. "The absence of a significant
effect is disappointing, but we know that pro-inflammatory cytokines, which
are elicited by the immune system in advanced illness, contribute heavily to
fatigue and depressive systems as well as [a shortened] survival."
The trial was funded by the Cancer Councils of New South Wales and South
Australia, National Health and Medical Research Council of Australia, Cancer
Institute of New South Wales, and Pfizer, Inc. Pfizer had no input into the
study's design or outcome.
An abstract of "Effect of Sertraline on Symptoms and Survival
in Patients with Advanced Cancer, but Without Major Depression: A
Placebo-Controlled Double-Blind Randomized Trial" is posted at<www.thelancet.com/journals/lanonc/article/PIIS1470204507701481/abstract?iseop...>.▪